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The victory allowed the 12th-ranked Gamecocks (22-6, 7-2 SEC), to win the weekend series.
After taking the middle game 8-7 on Saturday, the Bulldogs (15-13, 3-6) failed in their effort to win back-to-back road games for the first time in league play this season.
The Bulldogs scored in each of their first two at-bats. Luke Adkins slugged a massive home run to right center field in the first inning. An inning later, Russ Sneed added a round-tripper of his own.
Starter Tyler Whitney (0-1) took the loss for the Bulldogs, giving up five earned runs on two hits, while walking five in 21⁄3 innings of work.
South Carolina has defeated Mississippi State in five straight series in Columbia dating back to the 2000 season.
The Bulldogs host Jackson State at 6:30 p.m. Tuesday.